Plasmatic Klotho and FGF23 Levels as Biomarkers of CKD-Associated Cardiac Disease in Type 2 Diabetic Patients.

BACKGROUND: Research over the past decade has focused on the role of Klotho as a cardio protective agent that prevents the effects of aging on the heart and reduces the burden of cardiovascular disease CVD. The role of the interaction between fibroblast growth factor 23-(FGF-23)/Klotho in Klotho-mediated actions is still under debate. The main objective was to ascertain the potential use of plasmatic Klotho and FGF23 as markers for CKD-associated cardiac disease and mortality. METHODS: This was a prospective analysis conducted in an outpatient diabetic nephropathy clinic, enrolling 107 diabetic patients with stage 2⁻3 CKD. Patients were divided into three groups according to their left ventricular mass index and relative wall thickness. RESULTS: Multinomial regression analysis demonstrated that low Klotho and higher FGF-23 levels were linked to a greater risk of concentric hypertrophy. In the generalized linear model (GLM), Klotho, FGF-23 and cardiac geometry groups were statistically significant as independent variables of cardiovascular hospitalization (p = 0.007). According to the Cox regression model, fatal cardiovascular events were associated with the following cardiac geometric classifications; eccentric hypertrophy (p = 0.050); concentric hypertrophy (p = 0.041), and serum phosphate ≥ 3.6 mg/dL (p = 0.025), FGF-23 ≥ 168 (p = 0.0149), α-klotho < 313 (p = 0.044). CONCLUSIONS: In our population, Klotho and FGF23 are associated with cardiovascular risk in the early stages of CKD.

Pretreatment antithrombotic strategies in non-ST elevation acute coronary syndromes in contemporaneous clinical practice.

BACKGROUND: Pretreatment antithrombotic strategies in non-ST elevation acute coronary syndromes (NSTE-ACS) during hospitalization is still a matter of contention within the cardiology community. Our aim was to analyze in-hospital and one-year follow-up outcomes of patients with NSTE-ACS pretreated with dual antiplatelet therapy (DAPT) versus single antiplatelet therapy (SAPT). METHODS: A retrospective study was carried out with NSTE-ACS patients planned to undergo an invasive strategy and were included in the Portuguese Registry of ACS between 2018-2021. A composite primary outcome (in-hospital re-infarction, stroke, heart failure, hemorrhage, death) was compared regarding antiplatelet strategy (DAPT versus SAPT). Secondary outcomes were defined as one-year all-cause mortality and one-year cardiovascular rehospitalization. RESULTS: A total of 1469 patients were included, with a mean age of 66±12 years and 73.9% were male. DAPT regime was used in 38.2% and SAPT in 61.8% of patients. NSTE myocardial infarction was the most frequent presentation (88.5%). Revascularization after 24h occurred in 44.8% patients (63% of these after 48h). Enoxaparin was the anticoagulant more frequently used (45.1%). The primary outcome was more frequently observed in the SAPT group (10.4%, p=0.033), mainly driven by more ischemic events. Time until revascularization > 48h and SAPT regime were independent predictors of the primary outcome (OR 1.66, p=0.036 and OR 2.03, p=0.008, respectively). CONCLUSION: NSTE-ACS patients pretreated with SAPT had worse in-hospital outcomes. This difference can be probably explained by a delay in time until revascularization. Pretreatment DAPT strategy and crossover between heparins is still frequently used in clinical practice.

Klotho levels: association with insulin resistance and albumin-to-creatinine ratio in type 2 diabetic patients.

PURPOSE: The present study aimed at evaluating the relationship between Klotho levels and insulin resistance and albumin-to-creatinine ratio (ACR) in type 2 diabetic patients with CKD. METHODS: We conducted an observational, cross-sectional study in our outpatient diabetic nephropathy clinic from 2014 to 2016, enrolling a total of 107 type 2 diabetic patients with stage 2-3 CKD, with a mean age of 59 years. Several clinical and laboratorial parameters were evaluated, including those related to mineral and carbohydrate metabolism. RESULTS: The mean eGFR at baseline was 53.2 mL/min, and the mean levels of ACR and Klotho were 181.9 µg/mg and 331.1 pg/m, respectively. In the simple linear regression model, Klotho levels were correlated with age, phosphorus, PTH, ACR, HOMA, IL-6, FGF-23, OxLDL, eGFR and vitamin D levels. Applying a multivariate linear regression model, only the ACR, HOMA-IR, FGF-23 and vitamin D independently influenced the Klotho levels. In the generalized linear model, only the Klotho groups were statistically significant as independent variable (p = 0.007). The results show that the group 1 (<268) compared with group 3 (>440) had higher odds in the higher ACR (≥181), ORa = 3.429, p = 0.014. There were no statistically significant differences between Klotho groups 2 and 3, and the HOMA-IR obtained showed that group 1 (<268) had greater odds of HOMA-IR ≥2 when compared with group 3 (>440), ORa = 21.59, p = 0.017. CONCLUSIONS: Our results showed that Klotho levels are influenced by FGF23, vitamin D and insulin resistance. This suggests that Klotho levels might be affected by renal function as well as having a relevant role on insulin metabolism and ACR homeostasis.